Safety and Efficacy of Once‐daily Single Generic Fixed‐drug Combination Tablet of Tenofovir, Lamivudine and Efavirenz among HIV‐infected Thais

BackgroundGeneric fixed dose combinations (FDCs) of nucleoside reverse transcriptase inhibitors (NRTIs) and non‐nucleoside reverse transcriptase inhibitors (NNRTIs) is commonly used in resource‐limited settings to increase adherence to lifelong treatment. However, the cumulative evidence of the long‐term complications, particularly mitochondrial toxicity of NRTIs, especially stavudine (or zidovudine), brings about widespread use of tenofovir (TDF). This study was aimed to assess the efficacy and safety of a FDC comprising 300 mg tenofovir (TDF), 300 mg LAM and 600 mg efavirenz (EFV).MethodsA Phase II open‐label clinical trial was conducted at HIV‐NAT, Thai AIDS Research Center, Thai Red Cross from April 2010 to December 2011. Patients were eligible to enroll if they were either: 1) on TDF, LAM and EFV as separate tablets, for at least 6 months with an undetectable viral load (= switch arm) or 2) treatment‐naïve. Safety profiles, including liver and renal functions, were assessed at baseline, weeks 4, 12, 24 and 48. In switch group, mid‐dose TDF plasma concentrations were measured by HPLC at baseline and week 4 after a switch to single FDC tablet.ResultsA total of 100 patients were enrolled (51 naïve). Median age was 34 years and 30% were female. The median baseline CD4 cell count (IQR) was 512 (395–620) cells/L and 232 (164–284) cells/L for the switch arm and ARV‐naïve group, respectively. The median (IQR) log10 HIV‐1 RNA for ARV‐naïve group was 4.9 (4.2–5.3) copies/mL. By ITT analysis, the proportion of cases with HIV RNA<50 copies/mL was 93% and 92% at week 24 and 48, respectively. Only 1 confirmed virological failure at week 12 with NNRTI‐resistant mutations (A98G, K103N, V118I, E138Q, Y181C). The reported 3 SAEs (severe headache, infective endocarditis, cervical dysplasia) were found and one was possibly related to the study drug. There were 49 mild to moderate efavirenz‐related central nervous system events, occurring in first few days‐weeks. There were no statistically significant changes on renal function and liver enzymes. Mean plasma concentrations of all three drugs in FDC met the acceptable target levels.ConclusionThe generic FDC of TDF/3TC/EFV was well tolerated and efficacious. Our findings lend support to the use of this generic FDC as first‐line antiretroviral therapy in resource limited settings.